Tenascin, a novel six-armed extracellular-matrix glycoprotein, is expressed in a temporally and spatially restricted pattern during carcinogenesis in association with stromal-epithelial interactions. In this study, we have tested the hypothesis that tenascin expression depends upon the change of the cellular environment from in vitro to in vivo. The distribution and alterations in the expression of tenascin were compared between in vitro and in vivo studies in a variety of human epithelial- and nonepithelial-derived cell lines. When cell lines were transplanted into nude mice, all xenografts induced host-mouse-stroma-derived tenascin. Four carcinoma-derived cell lines and all sarcoma-derived lines, which secreted tenascin in vitro, were found to produce human tenascin after transplantation. Furthermore, three carcinoma-derived cell lines, A431, HEp-2, and MCF7, which did not synthesize tenascin in vitro, did synthesize human tenascin after transplantation. These tenascin nonproducing carcinoma cell lines did not express tenascin mRNA in vitro. The addition of TGF-beta 1 to the culture medium induced the synthesis and secretion of tenascin, but TGF-beta 2 and bFGF were less effective. TGF-beta 1 also induced other extracellular-matrix components, fibronectin and laminin. TGF-beta 1 did not induce tenascin in tenascin nonproducing carcinoma cell lines, such as WiDr and A549, in which human tenascin was not induced after transplantation. We have established an in vitro system in which tenascin is induced by the diffusible factor TGF-beta 1. This system could shed light on the mechanism of induction of human tenascin observed in vivo in tenascin nonproducing carcinoma cell lines.